Despite the widely acknowledged gender differences in the prevalence and clinical course of posttraumatic stress disorder (PTSD), there exists a paucity of data on the neurobiological mechanisms that explain these reported gender disparities in PTSD; therefore, better understanding of neurobiological sex differences has the potential to provide understanding of the neurobiology of PTSD and will also lead to improving interventions and services for males and females. We propose to recruit N=12 medication-free female patients with civilian PTSD, measure their CB1 receptor-selective radioligand [11C]OMAR volumes of distribution (VT), an equivalent of CB1 receptor expression using PET and compare them with 12 men with PTSD, as well as individually age, gender and BMI-matched controls with (TC, N=24) and without (HC, N=24) trauma history. This will answer the key question of this application if there exist a sex difference in stress responsiveness on a receptor level resultant in elevated CB1 protein expression in PTSD women in a PTSD circuit. PUBLIC HEALTH RELEVANCE: Better understanding of neurobiological sex differences has the potential to provide not only improved understanding of the neurobiology of PTSD but will also lead to improving interventions and services for males and females. We propose to recruit N=12 medication-free female patients with civilian PTSD, measure their [11C]OMAR volumes of distribution (VT), an equivalent of CB1 receptor density using positron emission tomography (PET) and compare them with 12 men with PTSD, as well as individually age, gender and BMI- matched controls with (TC, N=24) and without (HC, N=24) trauma history.